tbuckley/cabot-search huggingface dataset:
Application of natural language processing to assess the performance status documentation quality metric in patients with non–small-cell lung cancer.
Authors: Arash Maghsoudi, Yvonne H. Sada, Huili Zhu, Sudha Yarlagadda, Danielle Guffey, Sara Nowakowski, Ang Li, Javad Razjouyan
Journal: Journal of Clinical Oncology (2023)

e13582 Background: Performance status (PS) assessment is important for cancer prognosis and treatment decision-making. PS documentation for stage IV non-small cell lung cancer (NSCLC) is a quality measure for ASCO Quality Oncology Practice Initiative (QOPI) Certification Program. We used natural language processing (NLP) to extract PS from unstructured electronic medical records (EMR) clinical notes in patients with metastatic NSCLC to verify PS documentation compliance and disparities in PS documentation. Methods: We identified oncology progress notes of stage IV NSCLC patients from Harris Health System, which is an integrated comprehensive healthcare system for underserved patients in Houston, TX. All progress notes within 60 days of first oncology clinic visit date were filtered based on visit type and author type. A rule-based regular expression NLP algorithm was used to extract the PS, namely Eastern Standard Cooperative Group (ECOG) or Karnofsky Performance Status (KPS). A total of 400 oncology notes were randomly selected from 400 distinct patients and annotated by two clinician reviewers, and discrepancies were resolved by a senior clinician judge. The annotated notes were split randomly into 200 training notes and 200 validation notes, and the performance of the NLP algorithm was evaluated. We used logistic regression to analyze potential disparity in PS documentation. Results: We identified 15,239 progress notes from 757 stage IV NSCLC patients. The NLP algorithm accuracy validated on the test data was 99% with corresponding positive predictive values (PPVs) for ECOG PS 0, 1, 2, 3, 4 of 100%, 100%, 95%, 94%, 94%, respectively. The NLP algorithm identified 85% of patients with appropriate PS documentation (sensitivity 100%, specificity 91%, positive predictive value 98%, negative predictive value 100%). Logistic regression analyses showed no significant differences in association between PS documentation and race/ethnicity, language, or sex. Conclusions: We developed an internally validated NLP algorithm to extract PS from EMR clinical notes. Despite potential language barriers, the QOPI metric of &gt;75% PS documentation was met in our hospital system without significant disparities in clinical care. [Table: see text]
A phase 2 randomized study of magrolimab combination therapy in adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC): ELEVATE-TNBC.
Authors: Natalie Rainey, Rohit Joshi, Joanne Chiu, Ann Chen, Hao Wang, Jared Odegard, Estibaliz Lopez Rodrigo, Sylvia Adams
Journal: Journal of Clinical Oncology (2023)

TPS1130 Background: Improving outcomes in patients (pts) with TNBC remains a high unmet need. Immune checkpoint inhibitors (ICIs) + chemotherapy (chemo) is approved for newly diagnosed pts with PD-L1+ tumors. Further, single-agent sacituzumab govitecan (SG), a Trop-2–directed antibody-drug conjugate, is approved for pts with mTNBC who received ≥2 prior systemic therapies (≥1 for metastatic disease). However, more options are needed for pts with PD-L1–negative mTNBC and for those with disease progression on chemo ± ICI. Magrolimab is a monoclonal antibody that blocks CD47, a “don’t eat me” signal often overexpressed on TNBC cells. Magrolimab blockade of CD47 induces macrophage-mediated phagocytosis of tumor cells and has shown preclinical activity and promising clinical efficacy in hematologic malignancies. Certain chemos, including taxanes, enhance prophagocytic signals on tumor cells, which may lead to synergistic antitumor activity with magrolimab. This study is evaluating the safety, tolerability, and efficacy of magrolimab + nab-paclitaxel/paclitaxel or + SG in mTNBC. Methods: This open-label study has 2 cohorts (C) with safety run-in and phase (ph) 2 portions. Eligible pts are ≥18 y with measurable disease per RECIST 1.1. C1 pts have PD-L1–negative untreated mTNBC. C2 pts have mTNBC and received 1 prior line of therapy in the advanced setting, a taxane in the neoadjuvant/adjuvant or metastatic setting, and, if PD-L1+, an ICI. Exclusion criteria include active central nervous system disease, RBC transfusion dependence, and prior treatment with CD47/SIRPα-targeting agents. C1 assesses nab-paclitaxel/paclitaxel + magrolimab (safety run-in) or ± magrolimab (ph 2; randomized 1:1). C2 assesses magrolimab + SG (safety run-in and ph 2). In C1 safety run-in, magrolimab is given intravenously (IV) as a 1-mg/kg priming dose on day (D) 1 of cycle 1 to mitigate on-target anemia, followed by 30 mg/kg (cycle 1: D8, 15, 22; cycle 2: D1, 8, 15, 22; cycle 3+: D1, 15) (28-d cycles). In C2 safety run-in, pts receive a 1-mg/kg priming dose on D1, followed by 30 mg/kg (cycle 1: D8, 15; cycle 2: D1, 8, 15) and 60 mg/kg (cycle 3+: D1) (21-d cycles). The recommended ph 2 dose (RP2D) is determined in the safety run-in, with de-escalation if prespecified dose-limiting toxicity (DLT) criteria are met. Once RP2D is determined, the ph 2 cohorts will follow their respective dose schedules. Nab-paclitaxel/paclitaxel and SG are given IV per standard of care. The primary endpoints are incidence of DLTs, adverse events, and abnormal lab results by CTCAE v5.0 (safety run-in); progression-free survival by RECIST 1.1 (ph 2 C1); and confirmed objective response rate by RECIST 1.1 (C2; pooled safety run-in and ph 2). Planned enrollment is ≈144 pts. Clinical trial information: NCT04958785 .
A phase 3 study of gedatolisib plus fulvestrant with and without palbociclib in patients with HR+/ HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor plus a nonsteroidal aromatase inhibitor (VIKTORIA-1).
Authors: Sara A. Hurvitz, Fabrice Andre, Massimo Cristofanilli, Giuseppe Curigliano, Antonio Giordano, Hyo S. Han, Miguel Martin, Barbara Pistilli, Hope S. Rugo, Robert Wesolowski, Samuel Suzuki, Sarah Mutka, Igor Gorbatchevsky, Sibylle Loibl
Journal: Journal of Clinical Oncology (2023)

TPS1118 Background: Patients who receive frontline CDK4/6 inhibitor (CDK4/6i) therapy eventually experience disease progression. Resistance to CDK4/6i is likely a transient adaptive mechanism that may be reversed by inhibition of the PI3K/mTOR pathway. Thus, combination of CDK4/6i and PI3K/mTORi after disease progression on CDK4/6i could restore sensitivity to CDK4/6i and prevent activation of the PI3K/mTOR pathway. This hypothesis was evaluated in a Phase 1b study (Layman SABCS 2021) of gedatolisib (geda), a potent inhibitor of PI3K and mTOR. Subjects with HR+/HER2- ABC with prior CDK4/6i received geda (180 mg IV weekly for 3 weeks, then one week off) with palbociclib (palbo) and fulvestrant (FUL). Median PFS was 12.9 months with 63% overall response rate. Efficacy was observed regardless of PIK3CA mutation status (Wesolowski SABCS 2022). Geda was well tolerated, with few discontinuations due to treatment-related adverse events (4%). The most common AE was stomatitis; hyperglycemia of any grade occurred in 26% of patients. This preliminary data, dosing schedule, and study population characteristics form the basis for the Phase 3 trial, VIKTORIA-1 (NCT05501886). Methods: This Phase 3 multinational clinical trial will evaluate geda and FULwith or without palboin patients with HR+/HER2- ABC previously treated with any CDK4/6i in combination with a non-steroidal aromatase inhibitor (AI) therapy. Those without tumor PIK3CA mutations will be assigned to Study 1 (n=351) and randomized to Arm A (geda, palbo, and FUL), Arm B (geda and FUL), or Arm C (FUL). Those with PIK3CA mutations will be assigned to Study 2 (n=350) and randomized to Arm D (geda, palbo, and FUL), Arm E (alpelisib and FUL), or Arm F (geda and FUL). Key eligibility criteria include adults with confirmed metastatic or locally advanced breast cancer, any menopausal status, radiologically evaluable disease, and prior CDK4/6i treatment in combination with a non-steroidal AI. Prior hormonal therapy, including SERDs, is allowed. Key exclusion criteria include prior treatment with a PI3K, Akt, or mTOR inhibitor, prior treatment with chemotherapy for advanced disease, more than two lines of prior endocrine therapy, bone only disease with no soft tissue components, active CNS metastases, and type 1 diabetes or uncontrolled type 2 diabetes. The primary endpoint is PFS assessed by blinded independent central review per RECIST v1.1. Secondary endpoints included overall survival, safety and tolerability, ORR, duration of response, time to response, CBR, quality of life, and pharmacokinetics. The trial is open for enrollment. Clinical trial information: NCT05501886 .
Decentralized elements within oncology trials: Labcorp experience.
Authors: Alicia Rami, Maria Alcaide, Begona de las Heras, Laura Vidal, Joanna Pascual, Kurt Lumsden
Journal: Journal of Clinical Oncology (2023)

e13630 Background: The concept of digital health using Decentralized elements (DE) has rapidly gained acceptance due to the COVID-19 pandemic, moving clinical trials (CTs) to a more patient-centric model (PCM) with fewer site visits. The primary aims of DE are reducing patient burden, increasing enrolment and retention, maintaining quality of life, and decreasing overall trial cost. Methods: Between 2011 and 2022, Labcorp conducted 491 CTs which incorporated DE: telemedicine, electronic clinical outcome assessments (eCOA), electronic informed consent (eConsent) and mobile clinical services (MCS). All CTs were analyzed by therapeutic area, study phase (1-4) and country. Results: The COVID-19 pandemic increased the implementation of DE. However, digital health uptake between therapeutic area differed. Comparing Oncology with Neurology (higher increase in research), whilst eCOA was implemented most in Oncology, the Neurology MCS increase was over 50% since 2020. Overall, Big Pharma implemented ~1.5% more Decentralized elements, vs the biotech sector. The majority were phase 3, followed by phase 2, with MCS increasing its demand in phase 1. By country, USA, Spain, France, Germany and Canada dominated. The majority were hybrid CTs, with few completely virtual. Conclusions: Labcorp experience demonstrates that overall, the interest to implement DE in CTs continues to grow, promoting the transition to a PCM. Nevertheless, solutions like MCS still need to gain more acceptance in Oncology due to the added complexity and logistics and will require training of all stakeholders, as well as understanding the benefits and potential country-specific limitations. [Table: see text]
Screening for high frequency malignant disease (SHIELD).
Authors: HA NGUYEN, Lindsey Cotton, Erika Vento-Gaudens, Victoria M. Raymond, Craig Eagle
Journal: Journal of Clinical Oncology (2023)

TPS1610 Background: Insufficient adherence to guideline recommended cancer screening undermines the effectiveness of current modalities to improve cancer related outcomes, resulting in an unmet clinical need. Implementation of a convenient blood-based cancer screening option, utilizing a test with high sensitivity and specificity, has the potential to address this unmet need. We aim to evaluate the performance of a blood-based multi-cancer screening test in a population of screen eligible individuals across multiple cancer types, encompassing a diverse representation of racial and ethnic groups. Methods: SHIELD (Screening for High Frequency Malignant Disease; NCT#05117840) is a prospective, observational, multi-center basket study in the United States and Europe designed to recruit individuals undergoing screening across multiple cancer types. The study’s primary objective is to evaluate the performance of a blood-based multi-cancer screening test (GuardantLUNAR-2, Guardant Health, US) to detect cancer in screen-relevant individuals compared to the reference standard cancer screening modality. Each study cohort represents a unique cancer type(s). Eligible individuals consent to whole blood collection within 90 days of the standard of care screening for the respective cancer type. Clinical diagnoses, e.g., cancer, are made per standard of care. Primary outcomes: sensitivity, specificity, negative and positive predictive value of the blood-based multi-cancer screening test. Secondary outcomes: number of screen-detected cancers, early and late-stage screen-detected cancers per 1000 screened individuals. One- and two- year clinical outcomes are collected by implementing HIPAA compliant, patient-level linkage of trial data with real-world data sources (Medidata, USA) to which patients consent subsequent to main study consent. Cohort A: Lung cancer screening. Eligibility is aligned with USPSTF screening recommendations; age 50-80 years with &gt; 20 pack-year smoking history who are current smokers or quit within the past 15 years, without any history of cancer or preinvasive lung lesions, and without recent surgery or trauma. This cohort will enroll 9,000 subjects over 24 months at up to 120 global sites. This cohort was initiated in January 2022. As of January 2023, 94 study sites have been activated with 4,977 individuals consented and 4,866 individuals enrolled (defined as study blood sample collected). To date, 4679/4977 (94%) individuals consented to the linkage process. Cohort A is on track to meet enrollment targets by the end of 2023 and on track for final primary outcome data collection by December 2024. Clinical trial information: NCT05117840 .
Cytology-histology correlation, time to diagnosis and time to therapy when cytology is performed in addition to biopsies in malignant spinal lesions of previously unknown malignant disease.
Authors: Anne Marie Asemissen, Leon-Gordian Köpke, Annika Heuer, Lutz Welker, Martin Stangenberg, Andreas Lübke, Malte Schröder, Marc Dreimann, Carsten Bokemeyer, Lennart Viezens, Lara Krüger
Journal: Journal of Clinical Oncology (2023)

e14007 Background: Metastatic spinal lesions are the first manifestation of malignant disease in up to 30% of patients (pts). Spinal care, diagnostic evaluation and initiation of systemic therapy are crucial for outcome in pts with advanced cancer. Histopathology (HP) from bone specimens is time consuming and decalcification procedure can hamper diagnostic information. The additional evaluation of spinal lesions by cytopathology (CP) has the potential to reduce time to diagnosis (TTD) and time to therapy (TTT). Therefore, we performed simultaneous analysis of CP and HP specimens from suspected malignant spinal lesions to evaluate the diagnostic value of additional CP. This work was supported by the German Society for Spine Surgery (DWG). Methods: We obtained CP specimens by transpedicular, intralesional aspiration through a Yamshidi needle or touch preparation from solid tissue samples. CP and HP specimens from spinal lesions were evaluated in parallel in 54 pts (CP/HP group). We analyzed sensitivity and specificity of CP in reference to HP. Furthermore, we compared the TTD and TTT of CP/HP group with a retrospective cohort of 103 patients in whom only HP was performed (HP group). Results: The collection of CP samples was feasible without elongation of surgery time or any complications for the pts. In 52/54 (96%) pts a CP-specimen was successfully obtained. Of the 52 pts analyzed, multiple myeloma was diagnosed in 10 pts, solid malignancy in 34, 1 pt had lymphoma and 7 did not show malignancy. The most common solid malignancies were prostate cancer (n=9), breast cancer (n=5) and adenocarcinoma of the lung (n=5). The sensitivity and specificity of CP in reference to HP is 98% and 71%, respectively. The concordance of CP and HP in differentiating between hematologic or solid neoplastic lesions is 94.2%. TTD in the CP/HP group was significantly shorter compared to HP group (1.7±1.8 and 8.6±3.6 d, respectively; p&lt;0.001). In addition, TTT in the CP/HP group was significantly shorter than in the HP group (19.3±14.4 d and 31.4±24.7 d; p=0.003). In 24.1% of pts a specific tumor therapy was initiated based on CP diagnosis before obtaining the results of HP. Conclusions: The evaluation of CP from malignant spinal lesions shows high sensitivity and concordance with HP and reduced TTD and TTT. Therefore, CP in addition to HP from spinal lesions of suspected malignancy has the potential to improve quality of life and prognosis in pts with advanced cancer. We therefore recommend the implementation of additional CP to HP in previously undiagnosed malignant spinal lesions.
Influence of personal and socioeconomic factors on patient’s perception and experience of clinical trial participation at rural NCI designated comprehensive cancer center.
Authors: Muhammad Zubair Afzal, Bret Wankel, John P. Palmer, Soham Kale, Jonathan P. Pirruccello, Yuanzhen Cao, Flanklin E. Corea-Dilbert, Aditya Sharma, Ziyao Lu, Natasha Dhawan, Samer Ibrahim, Tayyaba Sarwar, Keisuke Shirai
Journal: Journal of Clinical Oncology (2023)

e13520 Background: Due to limited access to healthcare providers, lengthy travel times to clinics, and disadvantageous socioeconomic dynamics, patients in rural locations face significant challenges causing a low recruitment in clinical trials. However, there may be preconceived assumptions of a patient’s desire to participate in a trial leading to bias from healthcare organizations and thereby, decreased efforts in enrollment. Dartmouth Cancer Center is the smallest NCI designated comprehensive cancer center, serving rural New Hampshire and Vermont. In this study, we surveyed patients with cancer to assess their level of understanding of clinical trials, factors influencing patients’ willingness to enroll, and the difficulties faced after accrual in the trials. Methods: A 23 items anonymous questionnaire was distributed to the oncology patients at the outpatient clinic. The questions included demographics, socioeconomic status, time to travel, challenges faced in participating in the trials. Cox proportional regression analysis was done to identify factors influencing decision to participate in trials. Results: Among 93 respondents, 74% are within the age of 61 – 80 years, 64.45% are male and 74% are married, 51% are retired and 59.7% have household income of ≤$100,000. 32.2% of our respondents travelled over 1 hour to receive care. 73.3% of the respondents understood what it means to participate in a clinical trial. 91.8% are willing, yet only 40% were given an option to participate in a trial. Only 10.5% ever declined to participate. Additional cost, frequent travel, and possibility of receiving a placebo are the biggest factors in declining a participation. Up to 95% of the participants enrolled in a trial had positive experience and have the ultraistic motives. None of the socioeconomic or personal factors had any significant bearing on willingness to participate. Conclusions: Socioeconomic and regional factors have little bearing on a person's inclination to participate in clinical trials. There is a strong interest in understanding and enrolling in clinical studies. Cancer centers need to reduce the gap between patient interest in trials and actual trial participation.[Table: see text]
Differential benefit of capecitabine-based chemotherapy among TNBC subtypes in the context of the CBCSG010 study.
Authors: Junjie Li, Wenya Wu, Yunsong Yang, Wentao Yang, Shao Zhimin
Journal: Journal of Clinical Oncology (2023)

528 Background: Our previous study classified TNBCs into four mRNA subtypes, provided additional insights into TNBC heterogeneity and potential therapeutic options. Then we conducted a phase Ib/II subtyping-based and genomic biomarker-guided umbrella trial (FUTURE, NCT03805399 ), demonstrated the clinical benefit of subtyping-based targeted therapy for refractory metastatic TNBC. Here, we further evaluate the prognosis and predictive value of molecular classification in early TNBC in CBCSG010 trial (NCT01642771), which is a prospective, randomized phase III trial confirmed adding capecitabine to anthracycline-taxane-based adjuvant chemotherapy significantly improved survival in TNBC. Methods: Tumor tissues and pathological sections were retrospectively collected. Immunohistochemical (IHC) staining and hematoxylin and eosin (HE) staining were performed on paraffin-embedded sections to conduct TNBC IHC subtype staining. RNA-sequencing were performed to characterize the intrinsic molecular features of TNBC microenvironment. Results: 585 patients enrolled in the CBCSG010 trial, 450 patients had pathological sections, among which 207 patients achieved successfully stained sections. PDL1, CD8 and stromal tumor infiltrating lymphocytes (sTILs) were chosen for identified TNBC Immune enriched phenotype. Patients with ≥20% positive tumor cell proportion score (TPS) of PDL1, ≥10% positive cells of CD8, and ≥10% positive sTILs were significantly associated with better 5y-DFS (disease-free survival). Among Immune enriched TNBC, kaplan-Meier curves showed that DFS rates were 96.4% and 73.7% in the capecitabine and control groups. Transcriptome data was used to picture the immune microenvironment landscape, showed that “immune-hot” patients (immune cells or immune genes enriched) were more likely to benefit from capecitabine treatment. Conclusions: TNBC subtypes is significantly associated with DFS, with Immune enriched phenotype achieving the best outcome, and “immune-hot” patients are more likely to benefit from adjuvant capecitabine. Designing future clinical trials adding immunotherapy in adjuvant treatment of TNBC might base on molecular features.
Clinicopathological characteristics, evolution, treatment patterns and outcomes of hormone-receptor-positive/HER2-low-positive metastatic breast cancer: A retrospective analysis.
Authors: Biyun Wang, Shuhui You, Yannan Zhao
Journal: Journal of Clinical Oncology (2023)

e13058 Background: HER2-low positivity is more prevalent in breast cancers with positive hormone receptor (HR). Patients with HR-positive and low HER2 expression may have different prognosis and characteristics. Nevertheless, research focusing on HR-positive/HER2-low-positive breast cancer remains scarce. Methods: This study included 458 patients with HR-positive/HER2-negative metastatic breast cancer (HR+/HER2- MBC) who received first- or second-line endocrine therapy at the Fudan University Shanghai Cancer Center (FUSCC) between July 2010 and October 2022. Results: Clinicopathological characteristics, HER2 expression in primary and metastatic lesions, treatment patterns, and clinical outcomes of various therapies were compared between the HER2-low-positive and HER2-zero groups. 54.37% (249/458) of the HR+/HER2- MBC patients were HER2-low-positive. Comparable clinicopathological characteristics were observed in the HER2-low-positive and HER2-zero groups. PFS of first- and second-line endocrine treatment was comparable for HER2-low-positive and HER2-zero patients. When taking chemotherapy, the HER2-low-positive group had a shorter PFS than the HER2-zero group (median PFS: 8.64 vs. 9.03 months, p = 0.03). 41.79% (28/67) of HER2-zero primary tumors increased their HER2 score on biopsy, while 41.67% (35/84) of HER2-low-positive tumors became HER2-zero. Patients with an elevated HER2 IHC score from the primary tumor to the metastatic tumor had a longer PFS than those with constant HER2-low-positive status (median PFS: 11.99 months vs. 8.84 months, p = 0.02). Conclusions: HR-positive MBC patients with HER2-low and HER2-zero expression responded similarly to endocrine therapy. But HER2-low-positivity in HR-positive MBC may reduce chemotherapeutic effectiveness and HER2 heterogeneity should be taken into consideration.